Nucleic acid-protein condensates in innate immunity

Mammalian cells combat pathogens by diverse mechanisms. A key aspect of host defense is the pattern recognition receptors (PRRs) that recognize foreign nucleic acids and activate innate immune signaling pathways. Dysregulation of innate immunity is associated with both infectious diseases and chronic inflammatory conditions. Recent results argue that recognition of, and signaling from, foreign nucleic acids can be modulated by the concentration of PRRs and their nucleic acid ligands into RNA/DNA-protein co-condensates. Such condensates can affect the initiation of distinct cell death programs, proinflammatory signaling, host shutdown, and the innate immune response. Given these roles, hosts and pathogens have evolved to promote or antagonize PRR-nucleic acid condensation. Moreover, general ribonucleoprotein (RNP) granules such as stress granules and paraspeckles can either promote the formation of double-stranded RNA (dsRNA) and/or influence the response to foreign nucleic acids. Herein, we discuss advances in the field that address the relationship between RNA/DNA-protein co-condensates and innate immune regulation.